Detection of abundant megakaryocytes in pulmonary artery blood in lung cancer patients using a microfluidic platform. (November 2018)

• Record Type: Journal Article
• Authors: Dejima, Hitoshi; Nakanishi, Hayao; Kuroda, Hiroaki; Yoshimura, Mayumi; Sakakura, Noriaki; Ueda, Nanae; Ohta, Yuko; Tanaka, Rie; Mori, Sayomi; Yoshida, Tatsuya; Hida, Toyoaki; Sawabata, Noriyoshi; Yatabe, Yasushi; Sakao, Yukinori
• Is Part Of: Lung cancer. Volume 125(2018)
• Page Start: 128
• Page End: 135
• Publication Date: 2018-11
• Subjects: PAB pulmonary arterial blood -- PVB pulmonary venous blood -- PB peripheral blood -- Pap Papanicolaou -- ICC immunocytochemistry -- IHC immunohistochemistry -- IF immunofluorescence -- 3D 3-dimensional -- TPO thrombopoietin -- CK cytokeratin -- CTC circulating tumor cells; Circulating megakaryocytes -- Lung cancer patients -- Microfluidic device -- Pulmonary arterial blood -- Thrombopoiesis; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.09.011
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Lung was recently re-discovered as an organ for platelet production in mouse model. New cytology-based microfluidic device was developed for rare cell isolation. Abundant megakaryocytes were detected in pulmonary artery of lung cancer patients. Pulmonary megakaryocytes consist of immature and mature platelet producing cells. Lung plays a significant role in systemic thrombopoiesis in lung cancer patients. Abstract: Objectives: The lung was recently re-discovered as a hematopoietic organ for platelet production in mice. However, evidence for the role of the lung in thrombopoiesis in humans is still limited. In this study, we examined megakaryocytes in the pulmonary and systemic circulation, specifically in pulmonary arterial blood (PAB), venous blood (PVB) and peripheral blood using a newly developed microfluidic platform for rare cell isolation. Materials and methods: We analyzed 23 lung cancer patients who underwent surgery in our institute. PAB and PVB were obtained from the resected lung immediately after surgery. Blood samples were size-selected using a filtration-based microfluidic device and enriched rare cells on glass slide specimens were stained with Papanicolaou (Pap), immunocytochemistry (ICC), and immunofluorescence (IF). Lung tissues were also analyzed by immunohistochemistry. Results: Pap/ICC/IF showed the presence of abundant CD61+/cytokeratin- giant cells with a megakaryocyte lineage in PAB, but only a few in PVB. These megakaryocytes were found to consist of CD61+/CD41+ immature megakaryocytes and CD61+/CD41- mature megakaryocytes with the potential to produce platelets. These findings were confirmed by the conventional hematological analysis of blood smears stained with Giemsa. In analysis of lung cancer, CD61+ megakaryocytes were observed exclusively in the capillaries of non-cancerous tissue, whereas platelets were selectively observed in the tumor blood vessels of cancerous tissue. Conclusions: These results indicate that numerous megakaryocytes migrate from systemic bone marrows to accumulate in PAs and arrest of mature megakaryocytes in the capillaries of normal lung, suggesting the possibility that the lung plays a physiological role in the systemic thrombopoiesis in lung cancer patients.